Alkoxy benzoates of nu (hydroxy ethyl) and nu (hydroxy phenethyl) substituted amino alchols



Patented Apr. 8, 1947 a UNITED STATES PATENT, OFFICE ALKOXY BENZOATES OF N(HYDROXY ETHYL) AND N(HYDROXY PHEN- ETHYL) SUBSTITUTED AIVIINO ALCO- HOLS Walter G. Christiansen, Glen Ridge, and Sidney E.

Harris, Nutley, N. J assignors to E. R. Squibb &

Sons, New York, N. Y., a corporation of New York i No Drawing. Original application September 9,

1937, Serial No. 163,034. Divided and this application June 28, 1944, Serial No. 542,620

Claims. (Cl. 260-473) 1 r 2 This application is a division of our application benzene, and distilling the residue in vacuo yields Serial No. 163,034, filed September 9, 1937. the desired product as a thick, colorless oil, solu- This invention relates to, and has for its object ble in' dilute acids, and having a boiling point of the provision of, certain amino-alcohol esters of 218-225 C./8 mm. Its hydrochloride is very oxy-benzoic acids, and acid-addition salts there- 5 y p of, These esters have the general formula EXAMPLE 2 fi k 5- [N-ethyZ-N- (c-hydroxyethyl) -am mo] -ethyl es- (Lower alkyl)-0HrOCO-(alkylene)-N\ ter of p-n-butoxy-benzoic acid R 10 This compound is obtained in the same manner wherein R represents a member of the group mm as that of Example 1, except that p-n-butoxysisting of hydroxy-alkyl and hydroxy-aralkyL benzoyl chloride is used instead of the p-ethoxy- The compounds of this invention are valuable benzoyl chlorid and t e a ou of the e y therapeutic agents, being particularly efiective for diethanolamine used is 7 g. The desired product inducing local anesthesia. has a boiling point of 216-220 C./3 mm. Its hy- In the practice of this invention, an aracyl drochloride is hygroscopic, halide of the general formula EXAMPLE 3 i (Lower m y1)-CHiOOC-(h ogen) amino-ethyl ester of p-ethozcy-benzozc acid A mixture comprising 9.95 g. of phenacyl is reacted with an alcohol 0f the formula bromide, 4.4 g. ethylaminoethanol and. 100 cc. (alkyl) benzene is refluxed for three hours. On adding h 10 g. potassium carbonate a vigorous evolution of carbon dioxide ensues. The suspension is then 3 further refluxed for four hours, the mixture of whereinR has the above-designated meaning, to potassium bromide and potassium carbonate produce the desired ester. However, other methfiltered off, and the filtrate treated with a solu- Ods h in er d r d may be mploy to pr tion of hydrogen chloride in ether. The reddish d t e Co po s of the present invention. brown semisolid which separates out crystallizes,

The amino-esters of this invention are generand is filtered off, washed with ether and dried ally I'GCOVGZGd in the form 0f their addition-salts in a, acuum over calcium chloride, The extremewith hydrochloric acid. However, other acids ]y.hygroscopic substance fo ed is N phena,cy1 forming addition salts with amines may be used N-ethyl-amino-ethanol hydrochloride.

in place of hydrochloric; such acids are boric, 3 Amixture comprising 7.28 g. of N-phenacyl-N.. nitric, lactic, tartaric, citric, phosphoric, sulfuric, ethyl-amino-ethanol, 7.5 g. p-ethoxy-benzoyl Dicric, and picrolonic. The add t onmay be chloride, 30 cc. benzene and 8 g. potassium carconverted into the free bases in the usual manner. bonate is stirred and refluxed for five hours, fi]- The following examples are illustrative of the tel-ed, and the filt t treated with a solution of invention: 40 hydrogen chloride in ether, The impure mate- EXAMPLE 1 rial is then purified by crystallization from a chloroform-petroleum ether mixture. The white gg' g z zzg escrystalline substance obtained is the N-phenacyl- N-ethyl-amino-ethyl ester of p-ethoxy-benzoic 6.7 g. of B,B-dihydroxy-triethylamine is disacid (hydrochloride). solved in cc. of dry benzene; 14 g. of 0.9 g. of the above hydrochloride is dissolved tassium carbonate is suspended therein, and after in 60 cc. alcohol containing 0.3 g. platinum oxadding 9.2 g. of p-ethoxy-benzoyl chloride the ide. The mixture is shaken for eight hours under reactants are refluxed, with stirring, for two a pressure of 35 pounds of hydrogen; it is then hours. Filtering the reactants, evaporating the 50 filtered, the filtrateconcentrated to a small volnine and diluted with'ether. The brownish-white crystalline substance is filtered ofi, washed with ether and dried in a vacuum over calcium chloride, The substance is p-[N-ethyl-N-(p-phenylp-hydroxy-ethyl) l-amino-ethyl ester of p-ethoxy-b-enzoic acid (hydrochloride). The invention may be variously otherwise embodied, within the scope of the: appended! claims".

We claim: I 1. A compound of the group consisting of amino-esters of the general formula,

(imam onion-0H wherein R" represents an alkyl resi'due with 2 to 45 v CHzCEg 'cmcnaon 4 wherein R" represents an alkyl residue with 2 to 4 carbon atoms.

3. The hydrochloride 0f fi-[N-ethyl-N-(B-hydroxyethyl) -amino] -ethy1 p-ethoxy-benzoate.

4. The hydrochloride of ,B-IN-ethyl-N-(B-hydroxyethyl) -arnino] -ethy1 p-n-butoxy-benzoate.

5. The hydrochloride of g- [N-ethyl-N-(B-phem yI-B-hydroxyethyl) -amino-ethy1 .p -ethoxy-benzoate.

WALTER G. CHRISTIANSEN. SIDNEY E. HARRIS.

REFERENCES CITED The following references are of record in the file of this patent: I

' [UNITED STATES PATENTS Number Name Date 2,103,266 Lott Dec. 28, 1937 Wildman Aug. 8, 1916 OTHER REFERENCES Rohmann et a1., Archiv. der Phormazie, vol. 274 (1936), Pgs. -126.. 

